The long-term objective of the project is to probe the molecular mechanisms of synaptic transmission using a large number of Drosophila mutants that are defective in the responses of the postsynaptic neurons but not in those of the presynaptic neurons. The more immediate objectives are to complete projects now under way and to carry out systematic phenotypic characterizations of putative synaptic transmission-defective mutants. The projects now under way include (1) raising antisera against histidine decarboxylase peptides to determine the site of histamine synthesis and (2) cloning and characterizing the putative calmodulin and histamine receptor genes. Phenotypic characterization of the existing mutants will be carried out for the purpose of identifying a subset of mutants with interesting or interpretable phenotypes. The goal for this project period is to identify up to three complementation groups of such mutants and concentrate the lab's efforts on those mutants. Several possible cloning strategies are described. It is hoped that the combination of phenotypic analysis of the mutants and molecular analysis of the genes identified by the mutants would provide fresh insights into the mechanisms of synaptic transmission. Although it is now widely acknowledged that Drosophila is one of the premier organisms for molecular studies of biological processes, there have been virtually no previous attempts to systematically exploit the power of this organism in the molecular study of synaptic transmission. Insofar as synapses occupy a central position in all complex neural processes, detailed molecular elucidation of synaptic transmission, as envisioned in this proposal, it critically important in the eventual understanding of brain functions and behavior.